Primary ciliary dyskinesia 27

Summary

Primary ciliary dyskinesia 27 (MONDO:0014215) is a disease caused by DRC2 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: DRC2 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 219

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	primary ciliary dyskinesia 27
Mondo ID	MONDO:0014215
OMIM	615504
DOID	DOID:0110611
UMLS	C3809701
MedGen	816031
GARD	0015976
Is cancer (heuristic)	no

Also known as: CCDC65 primary ciliary dyskinesia · CILD27 · ciliary dyskinesia, primary, 27 · ciliary dyskinesia, primary, type 27 · primary ciliary dyskinesia caused by mutation in CCDC65 · primary ciliary dyskinesia type 27

Data availability: 219 ClinVar variants · 2 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › primary ciliary dyskinesia › primary ciliary dyskinesia 27

Related subtypes (58): ciliary discoordination due to random ciliary orientation, ciliary dyskinesia with transposition of ciliary microtubules, ciliary dyskinesia with defective radial spokes, ciliary dyskinesia with excessively long cilia, Stromme syndrome, primary ciliary dyskinesia 1, ciliary dyskinesia, primary, 36, X-linked, primary ciliary dyskinesia 2, primary ciliary dyskinesia 3, primary ciliary dyskinesia 4, primary ciliary dyskinesia 5, primary ciliary dyskinesia 6, primary ciliary dyskinesia 7, primary ciliary dyskinesia 8, primary ciliary dyskinesia 9, primary ciliary dyskinesia 10, primary ciliary dyskinesia 11, primary ciliary dyskinesia 12, primary ciliary dyskinesia 13, primary ciliary dyskinesia 14, primary ciliary dyskinesia 15, primary ciliary dyskinesia 16, primary ciliary dyskinesia 17, primary ciliary dyskinesia 18, primary ciliary dyskinesia 19, primary ciliary dyskinesia 20, primary ciliary dyskinesia 21, primary ciliary dyskinesia 22, primary ciliary dyskinesia 23, primary ciliary dyskinesia 24, primary ciliary dyskinesia 25, primary ciliary dyskinesia 26, primary ciliary dyskinesia 28, primary ciliary dyskinesia 29, primary ciliary dyskinesia 30, primary ciliary dyskinesia 32, primary ciliary dyskinesia 33, primary ciliary dyskinesia 34, primary ciliary dyskinesia 35, ciliary dyskinesia, primary, 46, ciliary dyskinesia, primary, 47, and lissencephaly, ciliary dyskinesia, primary, 48, without situs inversus, ciliary dyskinesia, primary, 39, ciliary dyskinesia, primary, 40, ciliary dyskinesia, primary, 41, ciliary dyskinesia, primary, 42, ciliary dyskinesia, primary, 43, ciliary dyskinesia, primary, 44, ciliary dyskinesia, primary, 45, ciliary dyskinesia, primary, 37, ciliary dyskinesia, primary, 38, ciliary dyskinesia, primary, 54, ciliary dyskinesia, primary, 49, without situs inversus, ciliary dyskinesia, primary, 50, ciliary dyskinesia, primary, 51, ciliary dyskinesia, primary, 52, ciliary dyskinesia, primary, 53, CFAP46-related primary ciliary dyskinesia

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

219 retrieved; paginated sample, class counts are floors:

100 uncertain significance, 71 likely benign, 19 benign, 15 pathogenic, 5 benign/likely benign, 4 likely pathogenic, 4 conflicting classifications of pathogenicity, 1 pathogenic/likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
1450804	NM_033124.5(DRC2):c.739del (p.Leu247fs)	DRC2	Pathogenic	criteria provided, single submitter
1905890	NM_033124.5(DRC2):c.469dup (p.Arg157fs)	DRC2	Pathogenic	criteria provided, single submitter
1959634	NM_033124.5(DRC2):c.904_905del (p.Val302fs)	DRC2	Pathogenic	criteria provided, single submitter
2053606	NM_033124.5(DRC2):c.699del (p.Asn232_Tyr233insTer)	DRC2	Pathogenic	criteria provided, single submitter
2156089	NM_033124.5(DRC2):c.195G>A (p.Trp65Ter)	DRC2	Pathogenic	criteria provided, single submitter
2820721	NM_033124.5(DRC2):c.205dup (p.Leu69fs)	DRC2	Pathogenic	criteria provided, single submitter
2916429	NM_033124.5(DRC2):c.968_971del (p.Val323fs)	DRC2	Pathogenic	criteria provided, single submitter
3620853	NM_033124.5(DRC2):c.339C>G (p.Tyr113Ter)	DRC2	Pathogenic	criteria provided, single submitter
3667024	NM_033124.5(DRC2):c.710_711del (p.Thr237fs)	DRC2	Pathogenic	criteria provided, single submitter
3688873	NM_033124.5(DRC2):c.966dup (p.Val323fs)	DRC2	Pathogenic	criteria provided, single submitter
474640	NM_033124.5(DRC2):c.494del (p.Glu165fs)	DRC2	Pathogenic	criteria provided, multiple submitters, no conflicts
4788719	NM_033124.5(DRC2):c.339C>A (p.Tyr113Ter)	DRC2	Pathogenic	criteria provided, single submitter
4789177	NM_033124.5(DRC2):c.805C>T (p.Gln269Ter)	DRC2	Pathogenic	criteria provided, single submitter
644753	NM_033124.5(DRC2):c.718C>T (p.Arg240Ter)	DRC2	Pathogenic	criteria provided, single submitter
649817	NM_033124.5(DRC2):c.658G>T (p.Glu220Ter)	DRC2	Pathogenic	criteria provided, single submitter
88685	NM_033124.5(DRC2):c.877_878del (p.Ile293fs)	DRC2	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
3367020	NM_033124.5(CCDC65):c.876T>G (p.Tyr292Ter)	CCDC65	Likely pathogenic	criteria provided, single submitter
1508617	NM_033124.5(DRC2):c.470+1G>A	DRC2	Likely pathogenic	criteria provided, single submitter
2053470	NM_033124.5(DRC2):c.301-2A>C	DRC2	Likely pathogenic	criteria provided, single submitter
4793393	NM_033124.5(DRC2):c.807+1G>C	DRC2	Likely pathogenic	criteria provided, single submitter
2166194	NM_033124.5(DRC2):c.913C>T (p.Arg305Ter)	DRC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
474641	NM_033124.5(DRC2):c.549A>G (p.Ile183Met)	DRC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
575527	NM_033124.5(DRC2):c.1196T>C (p.Ile399Thr)	DRC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
700072	NM_033124.5(DRC2):c.683A>T (p.Asp228Val)	DRC2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications
1003152	NM_033124.5(CCDC65):c.871C>T (p.Arg291Trp)	CCDC65	Uncertain significance	criteria provided, single submitter
1057879	NM_033124.5(CCDC65):c.*2dup (p.Ter485=)	CCDC65	Uncertain significance	criteria provided, single submitter
1306302	NM_033124.5(CCDC65):c.474G>C (p.Lys158Asn)	CCDC65	Uncertain significance	criteria provided, multiple submitters, no conflicts
1431507	NM_033124.5(CCDC65):c.1087G>T (p.Val363Leu)	CCDC65	Uncertain significance	criteria provided, single submitter
1516234	NM_033124.5(CCDC65):c.328G>A (p.Glu110Lys)	CCDC65	Uncertain significance	criteria provided, multiple submitters, no conflicts
411133	NM_033124.5(CCDC65):c.1370_1371del (p.Phe457fs)	CCDC65	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
DRC2	Definitive	Autosomal recessive	primary ciliary dyskinesia 27	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
DRC2	Orphanet:244	Primary ciliary dyskinesia

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
DRC2	HGNC:29937	ENSG00000139537	Q8IXS2	Dynein regulatory complex subunit 2	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
DRC2	Dynein regulatory complex subunit 2	Component of the nexin-dynein regulatory complex (N-DRC), a key regulator of ciliary/flagellar motility which maintains the alignment and integrity of the distal axoneme and regulates microtubule sliding in motile axonemes.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
DRC2	Other/Unknown	no		DRC1/2_N, DRC1/DRC2

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
bronchial epithelial cell	1
olfactory segment of nasal mucosa	1
right uterine tube	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
DRC2	179	broad	marker	right uterine tube, bronchial epithelial cell, olfactory segment of nasal mucosa

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
DRC2	1,261

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
DRC2	Q8IXS2	1

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 1 evidence-associated genes (0 with Reactome annotation).

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
regulation of cilium movement	1	4213.0×	9e-04	DRC2
cilium-dependent cell motility	1	1404.3×	0.001	DRC2
axonemal dynein complex assembly	1	1053.2×	0.001	DRC2
cilium assembly	1	73.6×	0.014	DRC2

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
DRC2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	DRC2

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
DRC2	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.